Comparing in vitro, in situ, and in vivo experimental data in a three-dimensional model of mammalian cochlear mechanics

Normal mammalian hearing is refined by amplification of the motion of the cochlear partition. This partition, comprising the organ of Corti sandwiched between the basilar and tectorial membranes, contains the outer hair cells that are thought to drive this amplification process. Force generation by outer hair cells has been studied extensively in vitro and in situ, but, to understand cochlear amplification fully, it is necessary to characterize the role played by each of the components of the cochlear partition in vivo. Observations of cochlear partition motion in vivo are severely restricted by its inaccessibility and sensitivity to surgical trauma, so, for the present study, a computer model has been used to simulate the operation of the cochlea under different experimental conditions. In this model, which uniquely retains much of the three-dimensional complexity of the real cochlea, the motions of the basilar and tectorial membranes are fundamentally different during in situ- and in vivo-like conditions. Furthermore, enhanced outer hair cell force generation in vitro leads paradoxically to a decrease in the gain of the cochlear amplifier during sound stimulation to the model in vivo. These results suggest that it is not possible to extrapolate directly from experimental observations made in vitro and in situ to the normal operation of the intact organ in vivo.

Case study of the effects of atmospheric aerosols and regional haze on agriculture: An opportunity to enhance crop yields in China through emission controls?

The effect of atmospheric aerosols and regional haze from air pollution on the yields of rice and winter wheat grown in China is assessed. The assessment is based on estimates of aerosol optical depths over China, the effect of these optical depths on the solar irradiance reaching the earth’s surface, and the response of rice and winter wheat grown in Nanjing to the change in solar irradiance. Two sets of aerosol optical depths are presented: one based on a coupled, regional climate/air quality model simulation and the other inferred from solar radiation measurements made over a 12-year period at meteorological stations in China. The model-estimated optical depths are significantly smaller than those derived from observations, perhaps because of errors in one or both sets of optical depths or because the data from the meteorological stations has been affected by local pollution. Radiative transfer calculations using the smaller, model-estimated aerosol optical depths indicate that the so-called “direct effect” of regional haze results in an ≈5–30% reduction in the solar irradiance reaching some of China’s most productive agricultural regions. Crop-response model simulations suggest an ≈1:1 relationship between a percentage increase (decrease) in total surface solar irradiance and a percentage increase (decrease) in the yields of rice and wheat. Collectively, these calculations suggest that regional haze in China is currently depressing optimal yields of ≈70% of the crops grown in China by at least 5–30%. Reducing the severity of regional haze in China through air pollution control could potentially result in a significant increase in crop yields and help the nation meet its growing food demands in the coming decades.

A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

A quantitative model of interphase chromosome higher-order structure is presented based on the isochore model of the genome and results obtained in the field of copolymer research. G1 chromosomes are approximated in the model as multiblock copolymers of the 30-nm chromatin fiber, which alternately contain two types of 0.5- to 1-Mbp blocks (R and G minibands) differing in GC content and DNA-bound proteins. A G1 chromosome forms a single-chain string of loop clusters (micelles), with each loop ∼1–2 Mbp in size. The number of ∼20 loops per micelle was estimated from the dependence of geometrical versus genomic distances between two points on a G1 chromosome. The greater degree of chromatin extension in R versus G minibands and a difference in the replication time for these minibands (early S phase for R versus late S phase for G) are explained in this model as a result of the location of R minibands at micelle cores and G minibands at loop apices. The estimated number of micelles per nucleus is close to the observed number of replication clusters at the onset of S phase. A relationship between chromosomal and nuclear sizes for several types of higher eukaryotic cells (insects, plants, and mammals) is well described through the micelle structure of interphase chromosomes. For yeast cells, this relationship is described by a linear coil configuration of chromosomes.

Rapid restoration of visual pigment and function with oral retinoid in a mouse model of childhood blindness

Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention has the potential to restore vision in otherwise incurable genetic retinal degenerations.

Structural model of cytochrome b559 in photosystem II based on a mutant with genetically fused subunits

Photosystem II is a reaction center protein complex located in photosynthetic membranes of plants, algae, and cyanobacteria. Using light energy, photosystem II catalyzes the oxidation of water and the reduction of plastoquinone, resulting in the release of molecular oxygen. A key component of photosystem II is cytochrome b559, a membrane-embedded heme protein with an unknown function. The cytochrome is unusual in that a heme links two separate polypeptide subunits, α and β, either as a heterodimer (αβ) or as two homodimers (α2 and β2). To determine the structural organization of cytochrome b559 in the membrane, we used site-directed mutagenesis to fuse the coding regions of the two respective genes in the cyanobacterium Synechocystis sp. PCC 6803. In this construction, the C terminus of the α subunit (9 kDa) is attached to the N terminus of the β subunit (5 kDa) to form a 14-kDa αβ fusion protein that is predicted to have two membrane-spanning α-helices with antiparallel orientations. Cells containing the αβ fusion protein grow photoautotrophically and assemble functional photosystem II complexes. Optical spectroscopy shows that the αβ fusion protein binds heme and is incorporated into photosystem II. These data support a structural model of cytochrome b559 in which one heme is coordinated to an α2 homodimer and a second heme is coordinated to a β2 homodimer. In this model, each photosystem II complex contains two cytochrome b559 hemes, with the α2 heme located near the stromal side of the membrane and the β2 heme located near the lumenal side.

A cooperative model for receptor recognition and cell adhesion: evidence from the molecular packing in the 1.6-A crystal structure of the pheromone Er-1 from the ciliated protozoan Euplotes raikovi.

The crystal structure of the pheromone Er-1 from the unicellular eukaryotic organism Euplotes raikovi was determined at 1.6 A resolution and refined to a crystallographic R factor of 19.9%. In the tightly packed crystal, two extensive intermolecular helix-helix interactions arrange the Er-1 molecules into layers. Since the putative receptor of the pheromone is a membrane-bound protein, whose extracellular C-terminal domain is identical in amino acid sequence to the soluble pheromone, the interactions found in the crystal may mimic the pheromone-receptor interactions as they occur on a cell surface. Based on this, we propose a model for the interaction between soluble pheromone molecules and their receptors. In this model, strong pheromone-receptor binding emerges as a consequence of the cooperative utilization of several weak interactions. The model offers an explanation for the results of binding studies and may also explain the adhesion between cells that occurs during mating.

Estudo da reação de epoxidação do óleo de soja em condição de remoção de calor máxima.

Óleo de soja epoxidado (OSE) é um produto químico há muito tempo utilizado como co-estabilizante e plastificante secundário do poli (cloreto de vinila) (PVC), ou seja, como um material que tem limitações na quantidade máxima que pode ser usada no composto de PVC. A sua aplicação como plastificante primário, ou seja, como o principal elemento plastificante no composto de PVC, e como base para outros plastificantes de fontes renováveis, tem aumentado nos últimos anos, principalmente devido a melhorias de desempenho e à redução do custo do OSE em comparação com plastificantes tradicionais. A reação de epoxidação do óleo de soja é bem conhecida e ocorre em duas fases líquidas, com reações em ambas as fases, e transferência de massa entre as fases. O processo industrial mais utilizado conta com formação in-situ do ácido perfórmico, através da adição gradativa do principal reagente, o peróxido de hidrogênio a uma mistura agitada de ácido fórmico e óleo de soja refinado. Industrialmente, o processo é realizado em batelada, controlando a adição do reagente peróxido de hidrogênio de forma que a geração de calor não ultrapasse a capacidade de resfriamento do sistema. O processo tem um ciclo que pode variar entre 8 e 12 horas para atingir a conversão desejada, fazendo com que a capacidade de produção seja dependente de investimentos relativamente pesados em reatores agitados mecanicamente, que apresentam diversos riscos de segurança. Estudos anteriores não exploram em profundidade algumas potenciais áreas de otimização e redução das limitações dos processos, como a intensificação da transferência de calor, que permite a redução do tempo total de reação. Este trabalho avalia experimentalmente e propõe uma modelagem para a reação de epoxidação do óleo de soja em condições de remoção de calor máxima, o que permite que os reagentes sejam adicionados em sua totalidade no início da reação, simplificando o processo. Um modelo foi ajustado aos dados experimentais. O coeficiente de troca térmica, cuja estimativa teórica pode incorrer em erros significativos, foi calculado a partir de dados empíricos e incluído na modelagem, acrescentando um fator de variabilidade importante em relação aos modelos anteriores. O estudo propõe uma base teórica para potenciais alternativas aos processos adotados atualmente, buscando entender as condições necessárias e viáveis em escala industrial para redução do ciclo da reação, podendo inclusive apoiar potenciais estudos de implementação de um reator contínuo, mais eficiente e seguro, para esse processo.

Handling of Uncertainty in Life Cycle Inventory by Correlated Multivariate Lognormal Distributions: Application to the Design of Supply Chain Networks

Poster presented in the 24th European Symposium on Computer Aided Process Engineering (ESCAPE 24), Budapest, Hungary, June 15-18, 2014.

Algorithm for Correcting the Keratometric Error in the Estimation of the Corneal Power in Eyes With Previous Myopic Laser Refractive Surgery

Purpose: To calculate theoretically the errors in the estimation of corneal power when using the keratometric index (nk) in eyes that underwent laser refractive surgery for the correction of myopia and to define and validate clinically an algorithm for minimizing such errors. Methods: Differences between corneal power estimation by using the classical nk and by using the Gaussian equation in eyes that underwent laser myopic refractive surgery were simulated and evaluated theoretically. Additionally, an adjusted keratometric index (nkadj) model dependent on r1c was developed for minimizing these differences. The model was validated clinically by retrospectively using the data from 32 myopic eyes [range, −1.00 to −6.00 diopters (D)] that had undergone laser in situ keratomileusis using a solid-state laser platform. The agreement between Gaussian (PGaussc) and adjusted keratometric (Pkadj) corneal powers in such eyes was evaluated. Results: It was found that overestimations of corneal power up to 3.5 D were possible for nk = 1.3375 according to our simulations. The nk value to avoid the keratometric error ranged between 1.2984 and 1.3297. The following nkadj models were obtained: nkadj= −0.0064286r1c + 1.37688 (Gullstrand eye model) and nkadj = −0.0063804r1c + 1.37806 (Le Grand). The mean difference between Pkadj and PGaussc was 0.00 D, with limits of agreement of −0.45 and +0.46 D. This difference correlated significantly with the posterior corneal radius (r = −0.94, P < 0.01). Conclusions: The use of a single nk for estimating the corneal power in eyes that underwent a laser myopic refractive surgery can lead to significant errors. These errors can be minimized by using a variable nk dependent on r1c.

MINLP Model for the Synthesis of Heat Exchanger Networks with Handling Pressure of Process Streams

This paper introduces a new mathematical model for the simultaneous synthesis of heat exchanger networks (HENs), wherein the handling pressure of process streams is used to enhance the heat integration. The proposed approach combines generalized disjunctive programming (GDP) and mixed-integer nonlinear programming (MINLP) formulation, in order to minimize the total annualized cost composed by operational and capital expenses. A multi-stage superstructure is developed for the HEN synthesis, assuming constant heat capacity flow rates and isothermal mixing, and allowing for streams splits. In this model, the pressure and temperature of streams must be treated as optimization variables, increasing further the complexity and difficulty to solve the problem. In addition, the model allows for coupling of compressors and turbines to save energy. A case study is performed to verify the accuracy of the proposed model. In this example, the optimal integration between the heat and work decreases the need for thermal utilities in the HEN design. As a result, the total annualized cost is also reduced due to the decrease in the operational expenses related to the heating and cooling of the streams.

Handling of Uncertainty in Life Cycle Inventory by Correlated Multivariate Lognormal Distributions: Application to the Design of Supply Chain Networks

In this work, we analyze the effect of incorporating life cycle inventory (LCI) uncertainty on the multi-objective optimization of chemical supply chains (SC) considering simultaneously their economic and environmental performance. To this end, we present a stochastic multi-scenario mixed-integer linear programming (MILP) coupled with a two-step transformation scenario generation algorithm with the unique feature of providing scenarios where the LCI random variables are correlated and each one of them has the desired lognormal marginal distribution. The environmental performance is quantified following life cycle assessment (LCA) principles, which are represented in the model formulation through standard algebraic equations. The capabilities of our approach are illustrated through a case study of a petrochemical supply chain. We show that the stochastic solution improves the economic performance of the SC in comparison with the deterministic one at any level of the environmental impact, and moreover the correlation among environmental burdens provides more realistic scenarios for the decision making process.

Inference of binding affinity from neuronal receptors in humans

Tese de mestrado, Bioinformática e Biologia Computacional (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2016

Ice-atmosphere interactions and sea ice predictability at multiple resolutions in the Community Earth System Model

Thesis (Master's)--University of Washington, 2016-06

Selection of species and provenances for low-rainfall areas: physiological responses of Eucalyptus cloeziana and Eucalyptus argophloia to seasonal conditions in subtropical Queensland

Responses of stomatal conductance (g(s)) and net photosynthesis (A) to changes in soil water availability, photosynthetic photon flux density (Q), air temperature (1) and leaf-to-air vapour pressure deficit (D) were investigated in 4-year-old trees of a dry inland provenance of Eucalyptus argophloia Blakely, and two dry inland provenances (Coominglah and Hungry Hills) and a humid coastal provenance (Wolvi) of Eucalyptus cloeziana F. Muell. between April 2001 and April 2002 in southeast Queensland, Australia. There were minimal differences in A, g, and water relations variables among the coastal and inland provenances of E. cloeziana but large differences between E. argophloia and E. cloeziana. E. argophloia and to a lesser extent the Hungry Hills (inland) provenance of E. cloeziana maintained relatively higher pre-dawn water potential (psi(pd)) during the dry season suggesting possible access to water at depth. Simple phenomenological models of stomatal conductance as a function of Q, T and D explained 60% of variation in gs in E. cloeziana and more than 75% in E. argophloia, when seasonal effect was incorporated in the model. A Ball-Berry model for net photosynthesis explained between 70 and 80% of observed variation in A in both species. These results have implications in matching the dry and humid provenances of E. cloeziana and E. argophloia to suitable sites in subtropical environments. (C) 2004 Elsevier B.V. All rights reserved.

Improving precision and reducing bias in biological surveys: estimating false-negative error rates

The use of presence/absence data in wildlife management and biological surveys is widespread. There is a growing interest in quantifying the sources of error associated with these data. We show that false-negative errors (failure to record a species when in fact it is present) can have a significant impact on statistical estimation of habitat models using simulated data. Then we introduce an extension of logistic modeling, the zero-inflated binomial (ZIB) model that permits the estimation of the rate of false-negative errors and the correction of estimates of the probability of occurrence for false-negative errors by using repeated. visits to the same site. Our simulations show that even relatively low rates of false negatives bias statistical estimates of habitat effects. The method with three repeated visits eliminates the bias, but estimates are relatively imprecise. Six repeated visits improve precision of estimates to levels comparable to that achieved with conventional statistics in the absence of false-negative errors In general, when error rates are less than or equal to50% greater efficiency is gained by adding more sites, whereas when error rates are >50% it is better to increase the number of repeated visits. We highlight the flexibility of the method with three case studies, clearly demonstrating the effect of false-negative errors for a range of commonly used survey methods.